BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the field of glaucoma therapy and more particularly to a laser-based system and technique for treating a patient's obstructed outflows pathways in the eye to enhance aqueous outflows and thereby lower intraocular pressure. The system and method introduces uniformly dimensioned nanoparticles into meshwork spaces to provide photoabsorption of a selected wavelength to thereby deliver energy directly to media and trabecular cords of the trabecular meshwork.
2. Description of Related Art
Glaucoma is a general term given to a group of debilitating eye diseases that afflict approximately 1%-2% of the U.S. population and an estimated 67 million people worldwide. In the U.S, the incidence of glaucoma rises with age to over 6% of the Caucasian population 75 years and older, and about 11% of the population of African descent 75 years and older. Glaucoma represents a significant health care issue, with millions of people worldwide at risk of vision loss.
The principal sign of glaucoma is elevated intraocular pressure (IOP) that ultimately can damage the optic nerve and result in impairment to, or loss of, normal visual function. Aqueous humor aq is the clear nutrient fluid that circulates within the anterior chamber ac of an eye to nourish ocular tissues. The aqueous aq is produced by the ciliary body cb and is drained through the trabecular meshwork tm and Schlemm's canal sch (see FIG. 1A). In a glaucoma condition, drainage of aqueous through the trabecular meshwork tm is insufficient to balance aqueous production, and therefore fluid intraocular pressure can be elevated and eventually damage the optic nerve.
Primary open-angle glaucoma is the most prevalent open-angle glaucoma in the U.S. representing approximately 37% of total U.S. cases, or about 1.2 million people, with an estimated 63,000 new cases annually. The pathophysiological mechanisms underlying primary open-angle glaucoma are not fully understood. It is believed that one or more factors play a role, for example, (i) that as a patient ages, the trabecular meshwork undergoes biostructural changes and loses its ability to regulate outflows, or (ii) that naturally elevated IOP levels can be tolerated initially, but after a long period begin to cause irreversible damage.
Another form of ocular hypertension is caused by exfoliation syndrome or exfoliation glaucoma. In this condition, the iris rubs against the lens and dislodges white flakes from the lens surface that are carried by the aqueous humor into the trabecular meshwork. It is believed that the exfoliated flakes build up in the trabecular meshwork and block outflow facility, eventually leading to a rise in IOP and full-blown glaucoma. This type of exfoliation glaucoma accounts for approximately 20% of total U.S. glaucoma cases or about 660,00 people. An estimated 34,000 new cases are diagnosed annually in the U.S.
Pigmentary glaucoma is caused by pigment dispersion syndrome wherein abrasive contact between the iris and lens sheds pigment into the anterior chamber and aqueous humor. The pigment again can clog the trabecular meshwork and increase IOP. Pigmentary glaucoma accounts for approximately 3% of total U.S. glaucoma cases or about 100,000 people with an estimated 5,000 new cases per year.
The ability of the trabecular meshwork in filtering aqueous flows plays a central role in many forms of glaucoma. The meshwork consists of about 25 layers of perforated trabecular sheets (ts1 . . . ts25) around the filtration angle of the anterior chamber ac, having a width of about 1,000 μm to 1,500 μm (1.0 mm. to 1.5 mm.) in a circumference ranging from 35,000 to 40,000 μm (see FIGS. 1A-1B). FIG. 1C shows an enlarged micrograph of trabecular cords and openings. FIG. 1E is a representation of the endothelial layer el of a trabecular cord tc or beam wherein its core comprises predominantly collagen microfibrils. FIG. 1D illustrates that each successively deeper trabecular sheet ts of the meshwork has smaller openings or pores p between trabecular cords tc than more superficial trabecular sheets. Further, the intrasheet spacing iss diminishes between successively deeper trabecular sheets ts. The meshwork thus serves as a filtration mechanism wherein cellular detritus and other debris in the aqueous flow is captured before it passes into Schlemm's canal sch wherein the outflows are carried away from the anterior chamber. FIG. 1D includes a graphic representation of exfoliated detritus indicated at d accumulating within spaces in the meshwork that are believed responsible for reducing outflow facility through the meshwork and for collapsing intrasheet spacing.
Various laser therapies have been developed or proposed for treating a patient's trabecular meshwork. These laser approaches rely on trans-corneal irradiation of a series of spots on the surface of meshwork tm exposed to the anterior chamber. The ophthalmologist utilizes a goniolens to direct the laser beam to strike exposed trabecular sheets at an oblique angle. For example, argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT) have been tested and compared in several trials. ALT was introduced in the 1980's and uses an argon laser operating at a wavelength (A) range of about 512 nm with a pulse duration of about 0.10 second to irradiate a series of about 50 spots only around 180° of the meshwork. The more recently developed trans-corneal laser approach, called SLT, uses a short-pulse 532 nm laser with pulse duration of 3-10 nanoseconds and energy levels that range from 0.60 mJ to 1.20 mJ. This approach was disclosed by Latina in U.S. Pat. No. 5,549,596. Yet another trans-corneal laser approach was disclosed by Hsia et al. in U.S. Pat. No. 6,059,772. Hsia disclosed three experimental trials on a limited set of human patients using an 800 nm laser beam with microsecond pulse durations, and varied energy levels. TABLE A below compares the laser parameters used in the various approaches, arranged in order of increasing wavelengths (λ).
|TABLE A |
| ||λ ||Pulse Duration ||Power ||Beam Size |
|ALT ||514 nm ||0.1 second (100 ms) ||various powers || 50 μm |
| || || ||settings |
|SLT ||532 nm || 3 ns-10 ns ||0.6-1.2 mJ/pulse ||300-400 μm |
|Hsia ||800 nm || 1 microsecond || 30-80 mJ/pulse ||100-200 μm |
|et al. |
A recent series of articles provides a comparative evaluation of ALT and SLT and investigates the mechanisms of action that underlie ALT and SLT to lower intraocular pressure (see Ocular Surgery News, Mar. 1, 2000). The results of these evaluations also can be instructive as to the probable mechanisms of action underlying the laser approach, if eventually proven under FDA regulatory schemes, that was proposed by Hsia in U.S. Pat. No. 6,059,772.
The ALT and SLT approaches use very similar wavelengths—514 nm for ALT vs. 532 nm for ALT. Still, as reported by Dr. J. Alvarado, the laser-tissue interactions in trabecular meshwork tissues of glaucoma patients differ markedly between ALT and SLT. (See Alvarado, J. A., Mechanical and Biological Comparison of ALT and SLT; Ocular Surgery News, Mar. 1, 2000). The ALT treatment modality produces a discrete burn or photocoagulation-type injury in trabecular sheets that are impacted by the laser irradiation. The damage is clearly visible to the ophthalmologist through a slit-lamp biomicroscope. In contrast to ALT, the SLT method produces no laser burns—the trabecular meshwork appears undamaged and without tissue reaction to the incident radiation. Dr. Alvarado stated that “[d]espite differences in the interaction of the laser light with the treated tissues, early clinical outcome comparisons of SLT and ALT have shown that the treatments are similar in the capacity to lower the intraocular pressure (IOP) of glaucoma patients.” Id. at p. 1. From TABLE A, it is readily apparent that the main difference between ALT and SLT is the pulse duration and the hence the energy delivered per pulse to the targeted tissue volume (e.g., fluence in J/cm2). The thermal relaxation time between laser pulses also is of critical importance, but was not discussed in detail in the Alvarado article referenced above.
In both ALT and SLT, the light emissions interact with the principal chromophore found in the trabecular meshwork, which in this case comprises melanin granules in the cytoplasm of endothelial cells lining the meshwork. While the ALT and SLT wavelengths target melanin, the pulse duration of SLT is so brief (in the range of 3 ns to 10 ns) that the energy absorption within, or vaporization of, the melanin polymer does not transfer significant thermal energy to surrounding connective tissue (i.e., collagen microfibrils in the trabecular cords) or other non-melanin containing cells. In contrast, ALT delivers very substantial amounts of energy in long 100 ms pulses to chromophore granules, which thus results in the transfer of thermal effects throughout the trabecular cord. The thermal relaxation time for such tissue in considered equal to about 1 ms—so that the ALT pulse duration alone exceeds the thermal relaxation time by a factor of 100. One aspect of the laser-tissue interaction underlying ALT that lowers IOP is related to the coagulation and shrinkage of connective tissues (i.e., collagen microfibrils) at the laser impact site. It is proposed that the net effect of shrinkage of trabecular cords and trabecular sheets by laser coagulation is to stretch and open trabecular spaces within meshwork portions proximate to the totally coagulated or melted tissues, thereby providing improved aqueous outflows through some portions of the meshwork. However, such locally beneficial effects come at the expense of “melting” other adjacent portions of the meshwork structure and even displacing Schlemm's canal. Since ALT causes such substantial biostructural alterations, the procedure is not considered to be repeatable over the patient's lifetime.
A second factor is proposed to play a role in ALT to improve outflows, which relates to macrophage recruitment. Small numbers or monocytes are continuously circulating within aqueous flows that exit the eye through the meshwork tm and Schlemm's canal. It is believed that these monocytes are activated and transformed into macrophages in response to a tissue injury as part of the body's wound healing response—as when an ALT incident beam strikes the meshwork causing damage around the absorbing or exploding chromophore. (See Alvarado, J. A., Murphy, C. G., Outflow obstruction in pigmentary and primary open angle glaucoma, Arch Ophthalmol. 110, 1769-1778 (1992)). Following ALT, it was observed that numerous macrophages engulfed the melanin granules and remnants thereof in the meshwork and cleared the detritus from the meshwork tissues by circulation through Schlemm's canal.
In SLT, a similar mechanism relating to macrophage recruitment is believed to predominate to improve aqueous outflows through the meshwork, thus lowering intraocular pressure. In animal studies, it was observed that an SLT treatment caused a five-fold to eight-fold increase in the number of monocytes and macrophages in the meshwork. Dr. Alvarado proposed that SLT-induced injury to meshwork cells caused by photon absorption in melanin results in the release of factors and chemoattractants that recruit macrophages in a manner similar to that observed in ALT treatments. (See Alvarado, J. A., Mechanical and Biological Comparison of ALT and SLT; Ocular Surgery News, p. 3, Mar. 1, 2000). The SLT treatment parameters selected by the author (Latina) of U.S. Pat. No. 5,549,596 resulted from testing 532 nm and 1064 nm q-switched Nd:Yag lasers and an argon (ALT) laser in trabecular cell cultures having melanin pigments introduced therein. It was found that ALT irradiation at several ms pulse durations would ablate cells proximate to the absorbing melanin pigments. Latina thereafter selected low fluences (obtainable with very short pulse q-switched Nd:Yag laser) to allow photon absorption by the chromophore and subsequent thermal relaxation (heat dissipation) between laser pulses to prevent gross disruption of other cells in the culture. (See Latina, M. A., Underlying Principles and Pre-Clinical Studies of SLT; Ocular Surgery News, Mar. 1, 2000). By this means, the ns pulses shown in TABLE A were selected for meshwork treatments which later became known as SLT.
In summary, the data indicates that laser-induced alteration of connective tissue macromolecules (i.e., shrinkage of trabecular cords) caused by the absorption and conduction of thermal effects throughout trabecular beam occurs in ALT—but not SLT. However, ALT and SLT both utilize a second mechanism for facilitating outflows—that is, the recruitment of macrophages that clean detritus from the meshwork following ALT and SLT incident radiation that is induced by the body's wound healing response.
Now turning to the treatment modality suggested by Hsia in U.S. Pat. No. 6,059,772, it is unknown whether the clinical experiments disclosed by Hsia will lead to commercialization of 800 nm lasers for specific meshwork treatments. However, it seems possible to predict with a reasonable level of confidence the exact nature of the laser-tissue interaction that will result from Hsia's treatment parameters, since the parameters are effectively bracketed by the ALT and SLT modalities of treatment.
In order to compare Hsia's approach to the well-documented ALT and SLT approaches, it first is necessary to describe in more detail the only true laser-tissue interaction that can serve as a therapeutic mechanism in meshwork treatments. All the methods listed in TABLE A rely on laser irradiation that is absorbed by the only chromophore (other than water) in the trabecular meshwork: melanin granules which are found in endothelial layers of the trabecular cords. Thus, by characterizing this chromophore's absorption characteristics in more detail, the mechanism of treating the meshwork can be understood to flow directly from the initial absorption, explosion or vaporization of melanin target.
Melanin is a complex material as it relates to photon absorption. The melanins formed from natural sources fall into two general classes: (i) eumelanin which is characterized as a brown to black insoluble composition (e.g., found in the retina, black hair, skin and certain other tissue epithelial and endothelial layers) and (ii) pheomelanin which is characterized as a yellow to reddish-brown alkali-soluble material (e.g., found in red hair). It is believed that naturally occurring melanin found in the trabecular meshwork falls only within the eumelanin class.
Such eumelanins are considered to be polymers that form links to other proteins. However, the details of the polymerization and the role of protein linkages in the natural melanin complex are not known. It is believed that insoluble melanins are highly polymeric cross-linked structures consisting of several hundred monomeric units. (See Prota, G., D'Ischia, M., Napolitano, A., The chemistry of melanins and related metabolites, in The Pigmentary System, ed. J. J. Nordlund et al., Oxford University Press, (1988)). Melanin granules are synthesized enzymatically at approximately 10 nm granular sites about the interior of a melanosome. A melanosome consists of an approximately 1 μm diameter organelle that can contain widely varied amounts of melanin. For example, the melanosomes of the retinal pigmented epithelium have a dense concentration of melanin. In contrast, cutaneous melanosomes are variable and may have as little as 10% of the melanin concentration of retinal melanosomes, while others can be altogether devoid of melanin. Moreover, the volume fraction (fv) of melanosomes in a particular epithelial layer, such as the cutaneous epidermis or retinal epithelium, varies greatly. The average absorption coefficient of a targeted volume depends on both the melanosomal μa (absorption coefficient) and the volume fraction (fv) of melanosomes in target. For example, in skin, the volume fraction of melanosomes is estimated at 1-3% for light skinned Caucasians; 11-16% for well-tanned Caucasians and Mediterraneans, and 18-43% for darkly pigmented Africans. It is believed that the trabecular cord epithelial layers carry a very small volume fraction (fv) of melanosomes, as evidenced by the fact that the structure is substantially translucent when viewed through a biomicroscope (see graphic representation of FIG. 1D).
Next, it is necessary to understand the average absorption coefficient μa (cm−1) for the interior of a melanosome that carries melanin granules or particles. In other words, the degree of in vivo photothermal or photomechanical effects in a targeted melanosome caused by a pulse of laser radiation comprises the critical mechanisms for evaluating any form of laser treatment of the trabecular meshwork. (In a collateral field, the amount of photons absorbed by a melanosome also can create oxidative reactions that are catalyzed by melanosomes exposed to blue or ultraviolet wavelengths).
FIG. 2 is a graphical representation of the μa of melanosomes based on several studies. Some studies investigated the threshold pulsed laser radiant exposure that causes vaporization of melanosomes to calculate the μa. For example, Jacques and McAuliffe used such vaporization to measure the μa of melanosomes in ex vivo human skin specimens, as well as literature data from similar in vivo measurements (see Jacques, S. L., McAuliffe, D. J., The melanosome: threshold temperature for explosive vaporization and internal absorption coefficient during pulsed laser irradiation. Photochem. Photobiol. 53:769-775 (1991)). In another study, Jacques, et al. used vaporization to measure the μa of melanosomes isolated from bovine retinal pigmented epithelium (see Jacques, S. L., Glickman, RD., Schwartz, J. A., Internal absorption coefficient and threshold for pulsed laser disruption of melanosomes isolated from retinal pigment epithelium. SPIE Proceedings 2681: 468-477 (1996)). The absorption coefficient μa of the melanosome interior of FIG. 2 also includes data based on optical measurements (see Goldman, L., The Skin, Arch. Environmental Health, 18:435, (1969); Sliney, D. H., Palmisano, W. A., The evaluation of laser hazards, AIHA Journal 20: 425 (1968)). To repeat, the concentration of melanin within melanosomes is quite variable, with ten-fold variation to be expected. However, the general shape of the melanosome absorption spectrum is approximated in FIG. 2 (see similar graph provided by S. Jacques at http://omlc.ogi.edu/spectra/melanin/jacques.mcauliffe.gif).
What is clear from the melanosome absorption coefficient and spectrum of FIG. 2 is that melanin has no sharp peaks and valleys common to some chromophores, such as when some close together wavelengths are highly absorbing and others are highly non-absorbing. In fact, the slope of the absorption spectrum FIG. 2 is smooth with somewhat higher absorption coefficients (lesser depth of photon penetration) at shorter wavelengths. The absorption spectrum of FIG. 2 shows that the 514 and 532 nm wavelengths of ALT and SLT, respectively, will be absorbed similarly for any given energy level. For this reason, at least one investigator thus far has opined that ALT would have an effect similar to SLT at lower power settings (see Alvarado, J. A., Mechanical and Biological Comparison of ALT and SLT; Ocular Surgery News, p. 3, Mar. 1, 2000). In fact, it seems clear from TABLE A—and the very slight difference in μa of melanin at 514 and 532 nm—that there can be no difference between ALT and SLT other than fluence (e.g., defined in mJ/cm2 of irradiated tissue).
Turning now to the question of the laser-tissue interaction proposed by Hsia in U.S. Pat. No. 6,059,772, it can be seen from FIG. 2 that laser irradiation at 800 nm will be substantially absorbed within melanosome organelles, although such a wavelength can penetrate more deeply in the melanosome than will 532 nm wavelengths. However, any series of tests of 800 nm irradiation of melanosomes at varied power levels should be able to reproduce the thermal effects of SLT—or ALT. In fact, the power levels (and hence fluences) proposed as effective by Hsia are higher than SLT power levels, and appear lower than ALT power levels. The laser tissue interactions caused by energy delivery within the Hsia parameters, when factoring in μa, spot size and pulse duration, seem effectively bracketed on the high side by ALT and the low side by SLT. Thus, the results of meshwork treatments under Hsia's parameters will be a laser-tissue interaction again bracketed by the proposed ALT and SLT mechanisms of action: (i) at a moderate energy fluences, the energy deposition in, and explosion of, some melanosomes will induce the body's wound healing response to increase monocytelmacrophage activity; and (ii) at higher energy fluences, the explosion or vaporization of melanosomes can be expected to alter the ultrastructure of the trabecular beams due to heat conduction throughout the beams.
According the Hsia disclosure, the energy delivery parameters at 800 nm shown in TABLE 1 apparently result in treatment effects similar to SLT—that is, no gross damage to meshwork cells or to the trabecular cord ultrastructure. The Hsia disclosure further describes a “non-preferred” set of treatment parameters tested in ex vivo experiments at higher energy levels (20 to 100 mJ with 100-200 micron spot sizes). In those experiments, the 800 nm laser irradiation caused significant thermally-induced modifications of meshwork ultrastructure, up to and including the ablation of holes in the meshwork-which is equivalent to ALT at high power levels. Thus, assuming the Hsia treatment parameters shown in TABLE 1 result in lowered IOP, the mechanisms of action almost certainly are the same as those underlying the ALT and SLT treatment modalities—simply depending on actual fluences selected to deliver to meshwork endothelial layers by modulation of power and spot sizes.
It is reasonable to question yet another aspect of the Hsia treatment parameters. The Hsia disclosure provides for relatively long (e.g., 1 ms) pulse durations at the wavelength of 800 nm that is absorbed by water far more greatly than ALT and SLT wavelengths. Water makes up about 90-95% of cornea tissue and substantially all of the aqueous humor. Transcorneal irradiation via a goniolens requires beam transmission though this predominantly water media before reaching the meshwork—a distance of several millimeters. The μa of water is about 0.022932 (cm−1) at 800 nm wavelength. The μa of water at the SLT wavelength of 532 nm is 0.000445 (cm−1), which differs by a factor of about 50 from the μa of at 800 nm. The result of this observation is that corneal burns could easily result from the Hsia treatment parameters, particularly since there are anecdotal reports of frequent corneal burns caused by SLT's wavelength—at a much lower μa and much shorter pulse duration.
A principal disadvantage of all prior art approaches described above is by targeting melanosomes in the trabecular meshwork—at low energy levels—any effects are probably limited to surface trabecular sheets. Only the trabecular sheets exposed to the incident beam absorb the beam's photonic energy. This factor suggests that only the first few sheets exposed to the anterior chamber ac are affected by such energy delivery (see FIG. 1A). The deeper meshwork sheets that are likely occluded with debris d (see FIG. 1D) likely remain unaffected by the direct laser irradiation at low power levels. This may explain why IOP can increase after SLT for a period of time in about 20% of patients, which seems to correspond to the time interval necessary for the monocyte/macrophage activity to increase.
None of the laser treatments described above directly target exfoliation debris d that accumulates in the trabecular meshwork and clogs meshwork pores p thereby reducing outflow facility. All of the above treatment modalities target the small volume fraction fv of melanosomes in meshwork endothelial layers since it is the only endogenous chromophore in the targeted trabecular beams. What is needed is a system and technique for directly delivering ablative energy to cellular detritus and other accumulations within trabecular spaces that will not damage the trabecular cords or meshwork sheets.
SUMMARY OF THE INVENTION
The present invention is adapted to non-invasively apply energy directly to media within spaces in a patient's trabecular meshwork to clear detitrus d that clogs the meshwork to thereby increase aqueous outflow facility. The systems and methods of the invention comprise a combination of (i) an exogenous chromophore introduced into the anterior chamber and localized in the deeper regions of the trabecular meshwork, and (ii) a laser system providing a selected coherent wavelength that is strongly absorbed by the exogenous chromophore particles. This system and method causes photoabsorption of energy by the chromophore nanometric particles, causing thermoelastic expansion therein that propagate bipolar stress waves within the fluid media to cause microcavitation. This localization of microcavitation in fluid that engulfs debris clogging the meshwork spaces can deliver sufficient mechanical energy to ablate the debris without causing significant damage to the trabecular meshwork sheets. In a preferred system embodiment, the chromophore nanocrystalline particles have an average diameter less than about 10-20 nm and are fabricated having a uniformity of dimension, purity level, and sphericity that allows for uniform photoabsorption of the selected coherent wavelength. Recent advances have enabled fabrication of such nanocrystalline particles by means of laser pyrolysis processes described in more detail below.
The systems and methods of the invention stand in clear contrast to all prior art laser irradiation methods that are used to treat the trabecular meshwork as described in the preceding section. All prior art modalities target melanosomes found in trabecular endothelial layers since it is the only endogenous chromophore. For several reasons, such prior art modalities cannot deliver substantial mechanical energy directly to fluids within meshwork spaces to ablate debris—unless very high energy levels are used which in turn would cause substantial damage to the meshwork.
First, all of the above-described prior art methods explode, vaporize or otherwise cause substantial thermal effects in melanosomes—which are embedded in an endothelial layer as depicted in FIG. 1E. At high energy levels in ALT, and at high power levels in the Hsia disclosure, the energy levels explode the melanosome thereby causing cavitation in the interior of the endothelial layer—which cannot be expected to cause any substantial propagation of energy (bipolar stress waves) to fluids at the exterior of the trabecular beams. In contrast, the method of the present invention localizes exogenous chromophores within fluids that engulf the debris clogging the meshwork. Second, the volume fraction (fv) of melanosomes in trabecular epithelial layers is very small, and therefore even high energy levels of that could explode melanosomes would probably result in slight energy propagation to the large volume of fluid media within the meshwork. In contrast, the method of the present invention can localize exogenous chromophores within the aqueous itself at a very high volume fraction (fv) when compared to endogenous melanosomes—the fv being perhaps greater by a factor of 100 to 1000. The high volume fv of chromophores also will allow lower fluences to cause the desired microcavitation, that in turn should not cause significant energy absorption by melanosomes. Third, the prior art methods that targeted melanosomes certainly have the highest energy absorption in surface trabecular sheets and endothelial layers that are struck be the laser beam. In contrast, the method of the present invention will localize the exogenous chromophore nanoparticles in deeper levels of the meshwork that are actually clogged with debris, thereby delivering energy directly to site of interest. Fourth, the method of the present invention, since it will not damage or destroy the ultrastructure of the meshwork, can be repeated over the patient's lifetime in a periodic treatment, for example annually or bi-annually which cannot be done with some prior art modalities such as ALT.
In sum, the method of the invention is adapted to cause bipolar stress waves and microcavitation in fluid media surrounding debris d that clogs the patient's trabecular meshwork to ablate such debris. The term debris is used interchangeably in this disclosure with the terms detritus, exfoliations and accumulations to refer to any types of cellular debris, lens flakes, iris pigments or any other materials known to be captured in meshwork pores. This disclosure uses the term ablate interchangeably with the terms disintegrate, obliterate and breakdown to mean the results of energy delivery to the debris that can dimensionally reduce or destroy the debris to allow it to be removed more rapidly form the meshwork via normal aqueous circulation.
The system and technique of the invention advantageously can ablate cellular detritus and other accumulations in a patient's trabecular meshwork by means of energy delivery to exogenous chromophores localized in the meshwork spaces.
The system and technique of the invention provides a non-invasive manner of directly delivering energy to media within meshwork spaces.
The system and technique of the invention treats a patient's trabecular meshwork without targeting and exploding melanosome granules embedded in trabecular endothelial layers.
The invention advantageously provides a volume of photoabsorbing nanoparticles that provide a high volume fraction fv of chromophores within the region of the debris targeted for ablation.
The system and technique of the invention advantageously provide means for causing greater energy delivery to deeper trabecular sheets rather that surface trabecular sheets.
The system and technique of the invention provides a non-invasive manner of delivering energy to media within meshwork spaces without causing significant thermal effects in the trabecular beams.
The invention advantageously provides a volume of microimplantables comprising nanocrystalline particles having a cross-section of less than about 100 nanometers.
The invention provides a microimplantables of nanocrystalline particles having a uniform dimension and purity to provide uniform energy absorption.
The system and technique of the invention advantageously provides a non-invasive manner of treating the patient's trabecular meshwork in a repeatable maintenance therapy that can continue over the patient's lifetime.